Evaluation of Serum Integrin αvβ3 &amp; Vitronectin in the Early Diagnosis of Breast Cancer

Radwan, Abdullah F.; Ismael, Omnia E; Fawzy, Amal; El‐Mesallamy, Hala O.

doi:10.7754/clin.lab.2019.181219

Cited by 12 publications

(8 citation statements)

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“…Previous studies have mentioned how Integrin αvβ3 works with vitronectin to promote cell adhesion and metastasis of tumors. Since vitronectin prominently accumulates in the ECM of tumor cells of various carcinomas, especially breast cancer cells [36]. This then allows vitronectin to bind with Integrin αvβ3, and then enhance angiogenesis and neovascularization of tissues.…”

Section: Plos Onementioning

confidence: 99%

Functional role of vitronectin in breast cancer

et al. 2020

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Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection. Vitronectin, a glycoprotein that is abundantly found in serum, extracellular matrix, and bone, binds to integrin αvβ3, and promotes cell adhesion and migration. Current studies indicate that patients with amplified vitronectin levels have lower survival rates than patients without amplified vitronectin levels. In this study, we focused on the role of vitronectin in breast cancer survival and its functional role as a non-invasive biomarker for early stage and stage specific breast cancer detection. To confirm that the expression of vitronectin is amplified in breast cancer, a total of 240 serum samples (n = 240), 200 from breast cancer patients and 40 controls were analyzed using the Reverse Phase Protein Array (RPPA) technique. Of the 240 samples, 120 samples were of African American (AA) descent, while the other 120 were of White American (WA) descent. Data indicated that there were some possible racial disparities in vitronectin levels and, differences also seen in the recurrent patient samples. Next, we tried to uncover the underlying mechanism which plays a critical role in vitronectin expression. The cellular data from four different breast cancer cell lines- MCF7, MDA-MB-231, MDA-MB-468, and HCC1599 indicated that the PI3K/AKT axis is modulating the expression of vitronectin. We believe that vitronectin concentration levels are involved and connected to the metastasis of breast cancer in certain patients, specifically based on recurrence or ethnicity, which is detrimental for poor prognosis. Therefore, in this current study we showed that the serum vitronectin levels could be an early marker for the breast cancer survival and we also determine the cellular signaling factors which modulate the expression and concentration of vitronectin.

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Section: Plos Onementioning

confidence: 99%

Functional role of vitronectin in breast cancer

et al. 2020

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“…It seems to anchor to ECM fibers and proteoglycans, and also disrupt cell adhesion, promoting spread and metastasis in NB [ 22 , 25 ]. Some studies have shown an important role for VN in initiation and progression of hepatic [ 26 ], breast [ 27 ] and lung [ 28 ] cancers, and its particular involvement in migration in ovarian cancer [ 29 , 30 ]. In a previous report we used inoculation of the NB cell lines studied here into the adrenal gland in VN knockout mice (VN-KO) to study the systemic role of VN in tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

López-Carrasco

Martín-Vañó

Burgos‐Panadero

et al. 2020

J Exp Clin Cancer Res

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Background Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK-mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.

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“…In addition to being a molecular targeted probe, integrins can also be used for cancer diagnosis and prognosis by directly detecting the expression level of specific integrins in serum or tissues. For example, integrin αvβ3 has been shown to be a potential diagnostic and prognostic biomarker in a variety of cancers, including gastric cancer ( Böger et al., 2015 ), breast cancer ( Radwan et al., 2019 ), glioblastoma ( Zhang et al., 2019 ), and lung cancer ( Schniering et al., 2019 ). It is worth noting that new anti-cancer therapies targeting integrins using nanoparticles as carriers are emerging.…”

Section: Current Cancer Therapeutic Strategies By Targeting Integrinsmentioning

confidence: 99%

The Biological Functions and Clinical Applications of Integrins in Cancers

Zhang

et al. 2020

Front. Pharmacol.

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Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumorassociated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

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Evaluation of Serum Integrin αvβ3 & Vitronectin in the Early Diagnosis of Breast Cancer

Cited by 12 publications

References 0 publications

Functional role of vitronectin in breast cancer

Functional role of vitronectin in breast cancer

Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line

The Biological Functions and Clinical Applications of Integrins in Cancers

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